GLUCOSE SENSITIVE MEMBRANES IN THE DELIVERY OF INSULIN

改善糖尿病患者的血糖调节胰岛素传递治疗 是这个项目的长期目标。葡萄糖敏感聚合物 膜(含胺基团和葡萄糖氧化酶)可膨胀和 已经制备了对胰岛素更具渗透性的药物。体内酸碱度 质子膜中葡萄糖酸的形成引起的减少 胺基团，引起静电斥力，随之而来的膨胀， 和增强胰岛素的渗透性。聚四氟乙烯的制备与表征 具有更高灵敏度和延伸性的新型葡萄糖敏感膜 作业范围，以及输送装置的设计和制造 结合这些膜可以控制胰岛素的传递 在生理条件下，建议的直接目标是 研究。将进行连续的、分段的研究计划， 把我们的精力集中在关键问题上 时间，按照它们的重要性顺序。为增强敏感性，做好准备 以及对经历大变化的“相变”聚合物的分析 在狭窄的PH值区间内的肿胀将在第一年完成。在第二年，我们 将开发提供更高氧气浓度的配置 膜，以扩大对葡萄糖的敏感范围。两种设计 将应用实现这一点的概念，并且每个概念的具体实施例 将根据预期业绩分析概念：1) “鼓”的概念：一个硅橡胶气囊，可从 组织，是在与葡萄糖敏感膜亲密接触时产生的。 2)二维02交付概念：硅橡胶管，带一个 葡萄糖敏感膜作为胰岛素传递的屏障将允许 径向02通过管壁传输。在第三年，设备 将最敏感的相变聚合物加入到 将做出允许足够的氧气渗透的配置，并 通过测量体外胰岛素释放率进行实验评估 一系列生理葡萄糖浓度。硅橡胶 试管/葡萄糖敏感膜设计用于两种 可能的方式：1)作为经常更换的短期种植体； 和2)作为连接到气体加压储气罐的导管的尖端 还有身体。这两种设备配置都特别 提出作为克服潜在限制的方法(由于酶 稳定性和生物相容性)之前的整体式、长期植入物 设计。

Improved treatment of diabetics with glucose regulated delivery of insulin is the long term goal of this project. Glucose sensitive polymeric membranes (containing amine groups and glucose oxidase) that swell and become more permeable to insulin have been prepared. An internal pH decrease caused by gluconic acid formation in the membrane protonates the amine groups, causing electrostatic charge repulsion, consequent swelling, and enhanced insulin permeation. The preparation and characterization of new glucose sensitive membranes with improved sensitivity and extended range of operation, and the design and fabrication of delivery devices incorporating these membranes that can control the delivery of insulin under physiological conditions, are the immediate goals of the proposed research. A sequential, segmented research program will be conducted, allowing concentration of our efforts on the critical problems one at a time, in their order of importance. To enhance sensitivity, preparation and analysis of "phase transition" polymers that undergo large changes in swelling over narrow pH intervals will be done in year 1. In year 2, we will develop configurations that provide higher oxygen concentration to the membrane to extend the range of sensitivity to glucose. Two design concepts to achieve this will be applied and specific embodiments of each concept will be analyzed with respect to expected performance: 1) The "drum" concept: a silicon rubber air sac,, replenishable from adjacent tissue, is created in intimate contact with the glucose sensitive membrane. 2) The two-dimensional 02 delivery concept: a silicone rubber tube with a glucose sensitive membrane as a barrier to insulin delivery will permit radial 02 transport through the walls of the tube. In year three, devices incorporating the most sensitive phase transition polymer in a configuration allowing sufficient oxygen permeation will be made and experimentally evaluated by measuring in vitro insulin release rates at a series of physiological glucose concentrations. The silicone rubber tube/glucose sensitive membrane designs are intended for use in two possible modes: 1) as short term implants that are replaced frequently; and, 2) as the tip of a catheter connected to a gas pressurized reservoir and the body. Both of these device configurations are specifically proposed as methods to overcome potential limitations (due to enzyme stability and biocompatibility) of previous monolithic, long term implant designs.